This invention relates to multiple electrode arrays for measuring electrophysiological activity and the fabrication of multiple electrode arrays of this type.
Planar multiple electrode arrays (MEAs) have become a widely used tool in neuroscience. Planar MEAs are typically employed in vitro to detect, in parallel, field potentials or unit activity from many locations in brain slices or cultures. Some of the most promising applications of MEA technology involve long-term activity recording from cell or slice cultures (see e.g., Gross et al., 1982, Recording of spontaneous activity with photoetched microelectrode surfaces from mouse spinal neurons in culture, J Neurosci Methods 5 13-22; Pancrazio et al., 2003, A portable microelectrode array recording system incorporating cultured neuronal networks for neurotoxin detection, Biosens Bioelectron 18 1339-47; Eytan et al., 2003, Selective adaptation in networks of cortical neurons, J Neurosci 23 9349-56; Morin et al., 2006, Constraining the connectivity of neuronal networks cultured on microelectrode arrays with microfluidic techniques: a step towards neuron-based functional chips, Biosens Bioelectron 21 1093-100; Chang et al., 2001, Modulation of neural network activity by patterning, Biosens Bioelectron 16 527-33; Nam et al., 2004, Patterning to enhance activity of cultured neuronal networks, IEEE Proc Nanobiotechnol 151 109-15; Uesaka et al., 2007, Interplay between laminar specificity and activity-dependent mechanisms of thalamocortical axon branching, J Neurosci 27 5215-23).
As the size of MEAs decrease, obtaining readings from MEAs with a high signal-to-noise ratio has proven to be increasingly difficult. On one hand, there is a drive to decrease the size of the electrodes to increase the spatial resolution of the MEAs. Unfortunately, as the diameter, size, and/or footprint of electrodes decrease, the impedance of the electrodes increases, which decreases the quality or sensitivity of the readings.
To attempt to minimize the impedance in the electrodes as they are reduced in size, many have added surface coatings to the tips of the electrodes. Design of these surface coatings has been a challenge as, in addition to lowering electrode impedance, these coatings should be stable in aqueous solutions and capable of being fabricated at low cost.
To date, the most commonly used coating is electrochemically deposited platinum black (see e.g., Jones et al., 1935, The measurement of the conductance of electrolytes. VII. On platinization. Journal of the American Chemical Society 57 280-4; Geddes, 1972, Electrodes and the Measurement of Bioelectric Events). While platinum black improves electrode impedance, it has the drawbacks of poor deposition reproducibility and durability. Some alternatives to platinum black include the use of ceramic materials as surface coatings such as porous titanium nitride (Bauerdick et al., 2003, BioMEMS Materials and Fabrication Technology, Biomedical Microdevices 5 93-9), porous silicon (Moxon et al., 2004, Nanostructured surface modification of ceramic-based microelectrodes to enhance biocompatibility for a direct brain-machine interface, IEEE Trans Biomed Eng 51 881-9), or conductive polymers (Cui X et al., 2001, Electrochemical deposition and characterization of conducting polymer polypyrrole/PSS on multichannel neural probes, Sensors and Actuators A 93 8-18; Yang and Martin, 2004, Microporous conducting polymers on neural microelectrode arrays II. Physical characterization, Sensors and Actuators A-Physical 113 204-11).
These materials, when used to fabricate the electrodes or to form a surface coating, lower electrode impedance. However, they frequently require sophisticated processing equipment leading to high chip costs, and sometimes suffer from poor reproducibility, process integration issues, and delamination (Cui and Martin, 2003, Fuzzy gold electrodes for lowering impedance and improving adhesion with electrodeposited conducting polymer films, Sensors and Actuators A-Physical 103 384-94).
In addition, current implantable neural interfaces have poor long-term stability. The underlying cause of this instability is not fully understood and is likely a combination of multiple factors, including local and systemic physiological responses to indwelling electrodes and failure attributed to device malfunction. In any event, neural interfaces typically have difficulty accurately detecting activity of the neural tissue as over time glial scaring can form at the attachment site of the electrodes and the electrodes may otherwise separate from the functional tissue. Several approaches, including integrated microfluidic channels for drug delivery and drug-eluting polymers, have been explored to suppress glial scar formation. However, due to the constraints with electrode footprint and impracticalities associated with microfabrication, most of these approaches are ineffective.
Hence, a need exists for an improved multiple electrode array that reduces impedance at the electrode tips while remaining functionally viable in a neural environment.